Thursday, July 30, 2009

Since its discovery just a few years ago, graphene has climbed to the top of the heap of new super-materials poised to transform the electronics and nanotechnology landscape.

As N.J. Tao, a researcher at the Biodesign Institute of Arizona State University explains, this two dimensional honeycomb structure of carbon atoms is exceptionally strong and versatile. Its unusual properties make it ideal for applications that are pushing the existing limits of microchips, chemical sensing instruments, biosensors, ultracapacitance devices, flexible displays and other innovations.

In the latest issue of Nature Nanotechnology, Tao describes the first direct measurement of a fundamental property of graphene, known as quantum capacitance, using an electrochemical gate method. A better understanding of this crucial variable should prove invaluable to other investigators participating in what amounts to a gold rush of graphene research.

Although theoretical work on single atomic layer graphene-like structures has been going on for decades, the discovery of real graphene came as a shock.

"When they found it was a stable material at room temperature," Tao says, "everyone was surprised."

As it happens, minute traces of graphene are shed whenever a pencil line is drawn, though producing a 2-D sheet of the material has proven trickier. Graphene is remarkable in terms of thinness and resiliency. A one-atom thick graphene sheet sufficient in size to cover a football field, would weigh less than a gram. It is also the strongest material in nature – roughly 200 times the strength of steel. Most of the excitement however, has to do with the unusual electronic properties of the material.

Graphene displays outstanding electron transport, permitting electricity to flow rapidly and more or less unimpeded through the material. In fact, electrons have been shown to behave as massless particles similar to photons, zipping across a graphene layer without scattering. This property is critical for many device applications and has prompted speculation that graphene could eventually supplant silicon as the substance of choice for computer chips, offering the prospect of ultrafast computers operating at terahertz speeds, rocketing past current gigahertz chip technology.

Yet, despite encouraging progress, a thorough understanding of graphene's electronic properties has remained elusive. Tao stresses that quantum capacitance measurements are an essential part of this understanding.

Capacitance is a material's ability to store energy. In classical physics, capacitance is limited by the repulsion of like electrical charges, for example, electrons. The more charge you put into a device, the more energy you have to expend to contain it, in order to overcome charge repulsion.

However, another kind of capacitance exists, and dominates overall capacitance in a two-dimensional material like graphene. This quantum capacitance is the result of the Pauli exclusion principle, which states that two fermions – a class of common particles including protons, neutrons and electrons – cannot occupy the same location at the same time. Once a quantum state is filled, subsequent fermions are forced to occupy successively higher energy states.

As Tao explains, "it's just like in a building, where people are forced to go to the second floor once the first level is occupied."

In the current study, two electrodes were attached to graphene, and a voltage applied across the material's two-dimensional surface by means of a third, gate electrode. In Tao's experiments, graphene's ability to store charge according to the laws of quantum capacitance, were subjected to detailed measurement.

The results show that graphene's capacitance is very small. Further, the quantum capacitance of graphene did not precisely duplicate theoretical predictions for the behavior of ideal graphene. This is due to the fact that charged impurities occur in experimental samples of graphene, which alter the behavior relative to what is expected according to theory.

Tao stresses the importance of these charged impurities and what they may mean for the development of graphene devices. Such impurities were already known to affect electron mobility in graphene, though their effect on quantum capacitance has only now been revealed. Low capacitance is particularly desirable for chemical sensing devices and biosensors as it produces a lower signal-to-noise ratio, providing for extremely fine-tuned resolution of chemical or biological agents.

Improvements to graphene will allow its electrical behavior to more closely approximate theory. This can be accomplished by adding counter ions to balance the charges resulting from impurities, thereby further lowering capacitance.

The sensitivity of graphene's single atomic layer geometry and low capacitance promise a significant boost for biosensor applications. Such applications are a central topic of interest for Tao, who directs the Biodesign Institute's Center for Bioelectronics and Biosensors.

As Tao explains, any biological substance that interacts with graphene's single atom surface layer can be detected, causing a huge change in the properties of the electrons.

One possible biosensor application under consideration would involve functionalizing graphene's surface with antibodies, in order to precisely study their interaction with specific antigens. Such graphene-based biosensors could detect individual binding events, given a suitable sample. For other applications, adding impurities to graphene could raise overall interfacial capacitance. Ultracapacitors made of graphene composites would be capable of storing much larger amounts of renewable energy from solar, wind or wave energy than current technologies permit.

Because of graphene's planar geometry, it may be more compatible with conventional electronic devices than other materials, including the much-vaunted carbon nanotubes.

"You can imagine an atomic sheet, cut into different shapes to create different device properties," Tao says.

Since the discovery of graphene, the hunt has been on for similar two-dimensional crystal lattices, though so far, graphene remains a precious oddity.

Bacteria know that they are too small to make an impact individually. So they wait, they multiply, and then they engage in behaviors that are only successful when all cells participate in unison. There are hundreds of behaviors that bacteria carry out in such communities. Now researchers at Rockefeller University have discovered one that has never been observed or described before in a living system.

In research published in the May 12 issue of Physical Review Letters, Albert J. Libchaber, head of the Laboratory of Experimental Condensed Matter Physics, and his colleagues, including first author Carine Douarche, a postdoctoral associate in the lab, show that when oxygen penetrates a sample of oxygen-deprived Escherichia coli bacteria, they do something that no living community had been seen to do before: The bacteria accumulate and form a solitary propagating wave that moves with constant velocity and without changing shape. But while the front is moving, each bacterium in it isn’t moving at all.

Unlike the undulating pattern of an ocean wave, which flattens or topples over as it approaches the shore, a soliton is a solitary, self-sustaining wave that behaves like a particle. For example, when two solitons collide, they merge into one and then separate into two with the same shape and velocity as before the collision. The first soliton was observed in 1834 at a canal in Scotland by John Scott Russell, a scientist who was so fascinated with what he saw that he followed it on horseback for miles and then set up a 30-foot water tank in his yard where he successfully simulated it, sparking considerable controversy.

The work began when Libchaber, Douarche and their colleagues placed E. coli bacteria in a sealed square chamber and measured the oxygen concentration and the density of bacteria every two hours until the bacteria consumed all the oxygen. (Bacteria, unlike humans, don’t die when starved for oxygen, but switch to a nonmotile state from which they can be revived.) The researchers then cracked the seals of the chamber, allowing oxygen to flow in.

The result: The motionless bacteria, which had spread out uniformly, began to move; first those around the perimeter, nearest to the seals, and then those further away. A few hours later, the bacteria began to spatially segregate into two domains of moving and nonmoving bacteria and pile up into a ring at the border of low-oxygen and no-oxygen. There they formed a solitary wave that propagated slowly but steadily toward the center of the chamber without changing its shape.

The effect, which lasted for more than 15 hours and covered a considerable distance (for bacteria), could not be explained by the expression of new proteins or by the addition of energy in the system. Instead, the creation of the front depends on the dispersion of the active bacteria and on the time it takes for oxygen-starved bacteria to completely stop moving, 15 minutes. The former allows the bacteria to propagate at a constant velocity, while the latter keeps the front from changing shape.

However, a propagating front of bacteria wasn’t all that was created. “To me, the biggest surprise was that the bacteria control the flow of oxygen in the regime,” says Libchaber. “There’s a propagating front of bacteria, but there is a propagating front of oxygen, too. And the bacteria, by absorbing the oxygen, control it very precisely.”

Oxygen, Libchaber explains, is one of the fastest-diffusing molecules, moving from regions of high concentration to low concentration such that the greater the distance it needs to travel, the faster it will diffuse there. But that is not what they observed. Rather, oxygen penetrated the chamber very slowly in a linear manner. Equal time, equal distance. “This pattern is not due to biology,” says Libchaber. “It has to do with the laws of physics. And it is organized in such an elegant way that the only thing it tells us is that we have a lot to learn from bacteria.”

It comes as no surprise that some babies are more difficult to soothe than others but frustrated parents may be relieved to know that this is not necessarily an indication of their parenting skills. According to a new report in Psychological Science, a journal of the Association for Psychological Science, children's temperament may be due in part to a combination of a certain gene and a specific pattern of brain activity.

The pattern of brain activity in the frontal cortex of the brain has been associated with various types of temperament in children. For example, infants who have more activity in the left frontal cortex are characterized as temperamentally "easy" and are easily calmed down. Conversely, infants with greater activity in the right half of the frontal cortex are temperamentally "negative" and are easily distressed and more difficult to soothe.

In this study, Louis Schmidt from McMaster University and his colleagues investigated the interaction between brain activity and the DRD4 gene to see if it predicted children's temperament. In a number of previous studies, the longer version (or allele) of this gene had been linked to increased sensory responsiveness, risk-seeking behavior, and attention problems in children. In the present study, brain activity was measured in 9-month-old infants via electroencephalography (EEG) recordings. When the children were 48 months old, their mothers completed questionnaires regarding their behavior and DNA samples were taken from the children for analysis of the DRD4 gene.

The results reveal interesting relations among brain activity, behavior, and the DRD4 gene. Among children who exhibited more activity in the left frontal cortex at 9 months, those who had the long version of the DRD4 gene were more soothable at 48 months than those who possessed the shorter version of the gene. However, the children with the long version of the DRD4 gene who had more activity in the right frontal cortex were the least soothable and exhibited more attention problems compared to the other children.

These findings indicate that the long version of the DRD4 gene may act as a moderator of children's temperament. The authors note that the "results suggest that it is possible that the DRD4 long allele plays different roles (for better and for worse) in child temperament" depending on internal conditions (the environment inside their bodies) and conclude that the pattern of brain activity (that is, greater activation in left or right frontal cortex) may influence whether this gene is a protective factor or a risk factor for soothability and attention problems. The authors cautioned that there are likely other factors that interact with these two measures in predicting children's temperament.

A newly identified gene appears to be highly predictive of not only the risk of developing Alzheimer's disease, but also the approximate age at which the disease will begin to manifest itself, according to researchers at Duke University Medical Center.

This new gene may be the most highly predictive gene discovered to date in Alzheimer's disease.

In findings presented today at the International Conference on Alzheimer's Disease, the gene TOMM40 was found to predict the age of Alzheimer's disease development within a five- to seven-year window among people over age 60.

"If borne out through additional research, a doctor could evaluate a patient based on age, especially among those over age 60, their APOE genotype and their TOMM40 status, to calculate an estimated disease risk and age of onset," said Allen Roses, MD, director of the recently established Deane Drug Discovery Institute and the study's lead author.

Roses earlier uncovered the association of apolipoprotein E (APOE) genotypes, particularly APOE4, with the risk and lower age of onset for Alzheimer's disease. This discovery remains one of the most confirmed genetic associations for any complex disease."It now looks fairly clear that there are two major genes -- APOE4 and TOMM40 -- and together they account an estimated 85-90 percent of the genetic effect," Roses said.

APOE4 accounts genetically for 50 percent of late onset cases of Alzheimer's disease but the other half remained a mystery. Genome-wide screening and other new techniques have been used repeatedly without success. Roses' team employed a different approach.

The APOE gene is present in all people and is characterized by three variants numbered two through four. The Duke researchers found that a variant of TOMM40 apparently evolved independently when attached to the APOE3 version of the gene than it did when attached to the APOE4 version.

Roses said the genetic association with Alzheimer's disease age of onset now goes beyond just APOE4. The researchers found that TOMM40 linked to APOE3 had either short or long repeated sequences, while all APOE4-linked repeat sequences were long. The study concluded that a longer version of TOMM40 attached to both APOE3 and APOE4 are significantly associated with an earlier disease onset, while the short repeat sequences were associated with a later onset of disease.

"Genome-wide screening detects big blocks of DNA inherited together, but it doesn't tell us all the differences within that block," Roses said. "We conducted a phylogenetic analysis to explore the evolution of the DNA and to see what changes take place on the backbone of other changes."

The technology has not been widely used in human genetics, Roses explained. "From all the genome-wide scans that were performed over the past four years, it was apparent that the variance within APOE could not account for the extremely high statistical significance which characterized this small block of genes, including APOE and TOMM40, which were inherited in a block."

"If someone gets APOE4 from their mother and APOE3 from their father, they also get TOMM40 as a linked caboose," Roses said. "If the TOMM40 is a short version of the gene attached to APOE3, then that person has a better chance of getting Alzheimer's disease very late, after age 80. But if it's a long TOMM40 they have a better chance of getting the disease before age 80."

The Duke team now plans to validate the association of the APOE genotypes and TOMM40 with age of disease onset and to determine how well these genes predict age of onset. They are planning a prospective, five-year study combined with a drug trial aimed at prevention or delay of disease onset.

The prevalence of Alzheimer's disease is predicted to quadruple world-wide by 2050 to more than 107 million cases, meaning that 1 in 85 persons will be living with the disease. It has been estimated that delaying disease onset by one or two years will decrease the disease burden in 2050 by 9.5 million or 23 million cases, respectively.

The research team also plans to use this type of phylogenetic analysis to uncover genetic associations in other diseases, including autism, diabetes and chronic obstructive pulmonary disease (COPD).

The brain's tendency to call upon these connections could help explain the curious phenomenon of "referred sensations," in which a person with an amputated arm "feels" sensations in the missing limb when he or she is touched on the face. Scientists believe this happens because the part of the brain that normally receives input from the arm begins "referring" to signals coming from a nearby brain region that receives information from the face.

"We found these referred sensations in the visual cortex, too," said senior author Nancy Kanwisher of the McGovern Institute for Brain Research at MIT, referring to the findings of a paper being published in the July 15 issue of the Journal of Neuroscience. "When we temporarily deprived part of the visual cortex from receiving input, subjects reported seeing squares distorted as rectangles. We were surprised to find these referred visual sensations happening as fast as we could measure, within two seconds."

Many scientists think that this kind of reorganized response to sensory information reflects a rewiring in the brain, or a growth of new connections.

"But these distortions happened too quickly to result from structural changes in the cortex," Kanwisher explained. "So we think the connections were already there but were silent, and that the brain is constantly recalibrating the connections through short-term plasticity mechanisms."

First author Daniel Dilks, a postdoctoral researcher in Kanwisher's lab, first found the square-to-rectangle distortion in a patient who suffered a stroke that deprived a portion of his visual cortex from receiving input. The stroke created a blind region in his field of vision. When a square object was placed outside this blind region, the patient perceived it as a rectangle stretching into the blind area - a result of the deprived neurons now responding to a neighboring part of the visual field.

"But the patient's cortex had been deprived of visual information for a long time, so we did not know how quickly the adult visual cortex could change following deprivation," Dilks said. "To find out, we took advantage of the natural blind spot in each eye, using a simple perceptual test in healthy volunteers with normal vision."

Blind spots occur because the retina has no photoreceptors where the optic nerve exits the eye, so the visual cortex receives no stimulation from that point. We do not perceive our blind spots because the left eye sees what is in the right eye's blind area, and vice versa. Even when one eye is closed, we are not normally aware of a gap in our visual field.

It takes a perceptual test to reveal the blind spot, which involves covering one eye and moving an object towards the blind spot until it "disappears" from view.

Dilks and colleagues used this test to see how soon after the cortex is deprived of information that volunteers begin to perceive shape distortions. They presented different-sized rectangles just outside the subjects' blind spot and asked subjects to judge the height and width at different time points after one eye was patched.

The volunteers perceived the rectangles elongating just two seconds after their eye was covered - much quicker than expected. When the eye patch was removed, the distortions vanished just as fast as they had appeared.

"So the visual cortex changes its response almost immediately to sensory deprivation and to new input," Kanwisher explained. "Our study shows the stunning ability of the brain to adapt to moment-to-moment changes in experience even in adulthood."

MIT researchers aim to change that with glues tailored to specific tissues. In a recent issue of Advanced Materials, they identified for the first time how one kind of glue material bonds to tissue and how that adhesion varies depending on the tissue involved, from the intestine to the lung. They then showed how by adjusting certain properties of the materials it was possible to create a range of adhesives optimized for specific tissues and applications.

"The delineation of tissue-specific mechanisms for material adhesion leads the way for tailoring materials to individual needs and applications. This exciting work may well change the clinical use and continued evolution of soft-tissue sealants and adhesive materials," said Elazer R. Edelman, principal investigator and MIT's Thomas D. and Virginia W. Cabot Professor of Health Sciences and Technology.

Adhesive sealants could improve patient care and reduce healthcare costs by cutting medical complications after surgery, such as leakage through incisions, and improved wound healing, according to Natalie Artzi, a postdoctoral associate who led the research in Edelman's lab.

Although there is already a billion-dollar market for such adhesives, "they haven't reached their true potential," Artzi said. Existing materials have limitations that often force doctors to compromise between adhesion strength and tissue reaction. For example, said Artzi, for a given tissue, the material may be adhesive but release toxins that could affect healing. Alternatively, the material could be quite tissue compatible, but degrade quickly, becoming non-adhesive. If the glue doesn't work, a doctor must switch to sutures or staples.

The problem, according to the MIT team is that while surgical adhesives rely on intimate interactions between the adhesive and the tissue in question, the properties of the target tissue have been largely ignored in designing adhesives. Instead, "one general formulation is proposed for application to the full range of soft tissues across diverse clinical applications," Artzi and colleagues wrote in their Advanced Materials paper.

The new work characterized a variety of interactions between one kind of glue (hyrogels composed of polyethylene glycol and dextran aldehyde, or PEG: dextran for short) and tissue from a rat's heart, lung, liver and duodenum (the first section of the intestine). The team found, for example, that the glue worked well with tissue from the duodenum, but poorly with that from the lung.

They then went on to "identify the functional groups in the material that are responsible for adhesion with tissue functional groups, and created a model to optimize adhesion for each tissue," Artzi said. In particular the paper explains how variation of chemical reactive groups in the material could be matched to the variability in the density of respective reactive groups on different tissues to regulate tissue-material interaction.

The team will use these findings to "develop a platform of adhesive materials" for specific tissues. Although it could take three to five years before the work translates into a product, "the concept is there," she concluded.